Influenza vaccine failure in the tropics: a retrospective cohort study of waning effectiveness.

Influenza vaccine effectiveness (VE) wanes over the course of a temperate climate winter season but little data are available from tropical countries with year-round influenza virus activity. In Singapore, a retrospective cohort study of adults vaccinated from 2013 to 2017 was conducted. Influenza vaccine failure was defined as hospital admission with polymerase chain reaction-confirmed influenza infection 2-49 weeks after vaccination. Relative VE was calculated by splitting the follow-up period into 8-week episodes (Lexis expansion) and the odds of influenza infection in the first 8-week period after vaccination (weeks 2-9) compared with subsequent 8-week periods using multivariable logistic regression adjusting for patient factors and influenza virus activity. Records of 19 298 influenza vaccinations were analysed with 617 (3.2%) influenza infections. Relative VE was stable for the first 26 weeks post-vaccination, but then declined for all three influenza types/subtypes to 69% at weeks 42-49 (95% confidence interval (CI) 52-92%, P = 0.011). VE declined fastest in older adults, in individuals with chronic pulmonary disease and in those who had been previously vaccinated within the last 2 years. Vaccine failure was significantly associated with a change in recommended vaccine strains between vaccination and observation period (adjusted odds ratio 1.26, 95% CI 1.06-1.50, P = 0.010).

Latent tuberculosis in patients with diabetes mellitus: prevalence, progression and public health implications.

BACKGROUND: Diabetes mellitus (DM) confers a higher risk for tuberculosis (TB). Yet, TB screening and chemoprophylaxis for latent TB infection (LTBI) in DM remains controversial. We conducted a cross-sectional study to elucidate LTBI prevalence and longitudinal follow-up to ascertain LTBI to active TB progression rate in DM. METHODS: 220 DM patients without previous TB from the outpatient diabetes clinic of the hospital were enrolled. T-Spot TB, tuberculin-skin-test (TST) and chest radiography (CXR) were performed. LTBI was defined by negative CXR with reactive T-Spot TB. Progression to active TB was confirmed by cross-checking against the TB registry. RESULTS: The prevalence of LTBI was 28.2% (62/220) by reactive T-Spot. None progressed to active TB from 2007-2013. Multivariate analysis revealed that any co-morbidity (p=0.016) was positively associated while metformin (p=0.008) was negatively associated with LTBI. CONCLUSIONS: Over a quarter of DM patients harbor LTBI. While the lack of demonstrable progression to active TB within the follow-up time frame up to this point does not unequivocally support a routine TB screening policy or anti-TB chemoprophylaxis for LTBI in a diabetic population for now, this preliminary evidence needs re-evaluation with longer follow-up of this enrolled cohort over the next decade.

Audit and improve! Evaluation of a real-time probe-based PCR assay with internal control for the direct detection of Mycobacterium tuberculosis complex.

We retrospectively audited the performance of the commercial kit in use in our laboratory for the detection of Mycobacterium tuberculosis complex (MTBC) and found the sensitivity to be unacceptably low at 69% (52/75). We developed an in-house end-point polymerase chain reaction (PCR) detecting IS6110, an IS-like element of MTBC, and achieved a sensitivity of 90% (66/73) with the same DNA samples, re-emphasising the poor performance of the commercial kit. In order to avoid specificity issues surrounding gel-based PCR, we developed a probe-based real-time PCR assay with an internal control and achieved a sensitivity of 84%, specificity of 97% and diagnostic odds ratio (DOR) of 207. The evaluation was performed on clinically requested samples, so we expect the performance of the assay in real life to match the data from this evaluation. Centers for Disease Control and Prevention (CDC) guidelines recommending nucleic acid tests for the investigation of possible cases of tuberculosis are expected to promote the use of molecular assays. It is important that clinical laboratories do not assume that assays, in-house or commercial, will perform well or that they will continue to perform well. Audit at regular intervals is necessary to maintain confidence and to demonstrate that the assay works to specification in the real test population.

Tuberculosis treatment effect on T-cell interferon-gamma responses to Mycobacterium tuberculosis-specific antigens.

The hypothesis that T-cell interferon-gamma responses to Mycobacterium tuberculosis-specific antigens decline as disease activity diminishes with tuberculosis (TB) treatment has generated interest in the interferon-gamma release assays (IGRAs) as treatment-monitoring tools. We studied the effect of TB treatment on these responses as measured by the QuantiFERON-TB Gold In-tube (QFT-IT) and T-SPOT.TB assays. 275 sputum culture-positive, HIV-uninfected pulmonary TB patients were tested with QFT-IT and T-SPOT.TB at baseline, treatment completion and 6 months thereafter. The QFT-IT was also performed at the end of the intensive phase. The time-treatment effect on the qualitative and quantitative IGRA results was determined. There were significant declines in the positivity rates and quantitative results of both IGRAs with treatment. The QFT-IT positivity rate was significantly lower than the T-SPOT.TB. The test reversion rate was significantly different for the two assays (13.9% for T-SPOT.TB versus 39.2% for QFT-IT). 79% and 46% tested positive with T-SPOT.TB and QFT-IT respectively at 6 months post-treatment completion. The kinetics of the quantitative responses was not significantly different between subjects with and without risk factors for disease relapse. That a substantial proportion of patients remained test-positive after TB treatment would suggest a limited role of IGRAs as treatment monitoring tools.

Brucellosis in a Singaporean with prolonged fever.

Brucellosis, a zoonotic disease of worldwide distribution, is common in many developing countries as well as in countries of the Mediterranean basin. We report brucellosis in a 52-year-old man, who had a recent travel history to Saudi Arabia, and who presented with prolonged fever and deranged liver enzymes. In view of the rarity of brucellosis and its potential life-threatening complications, patients returning from an endemic country need to be questioned for possible Brucella exposure, to ensure that diagnostic tests and treatment are carried out in a timely fashion. In addition to notifying the authorities, the clinician should also warn the laboratory early as cultures of brucellosis are highly transmissible and are one of the most common laboratory-acquired infections.

Use of a T cell interferon-gamma release assay to evaluate tuberculosis risk in newly qualified physicians in Singapore healthcare institutions.

BACKGROUND: Surveillance for latent tuberculosis in high-risk groups such as healthcare workers is limited by the nonspecificity of the tuberculin skin test (TST) in BCG-vaccinated individuals. The Mycobacterium tuberculosis antigen-specific interferon-gamma release assays (IGRAs) show promise for more accurate latent tuberculosis detection in such groups. OBJECTIVE: To compare the utility of an IGRA, the T-SPOT.TB assay, with that of the TST in healthcare workers with a high rate of BCG vaccination. METHODS: Two hundred seven medical students from 2 consecutive cohorts underwent the T-SPOT.TB test and the TST in their final year of study. Subjects with negative baseline test results underwent repeat testing after working for 1 year as junior physicians in Singapore's public hospitals. RESULTS: The baseline TST result was an induration 10 mm or greater in diameter in 177 of the 205 students who returned to have their TST results evaluated (86.3%), while the baseline T-SPOT.TB assay result was positive in 9 (4.3%) of the students. Repeat T-SPOT.TB testing in 182 baseline-negative subjects showed conversion in 9 (4.9%). A repeat TST in 18 subjects with baseline-negative TST results did not reveal any TST result conversion. CONCLUSIONS: The high rate of positive baseline TST results in our BCG-vaccinated healthcare workers renders the TST unsuitable as a surveillance tool in this tuberculosis risk group. Use of an IGRA has enabled the detection and treatment of latent tuberculosis in this group. Our T-SPOT.TB conversion rate highlights the need for greater tuberculosis awareness and improved infection control practices in our healthcare institutions.

Primary drug resistance and transmission analysis of HIV-1 in acute and recent drug-naïve seroconverters in Singapore.

OBJECTIVES: The aim of the study was to elucidate primary drug resistance and transmission of HIV-1 in acute and recent drug-naïve seroconverters in Singapore. METHODS: Acute and recent HIV-1 seroconverters were enrolled in the study. The HIV-1 polymerase (pol) gene was sequenced and used for genotypic drug resistance analysis and phylogenetic analysis. HIV-1 transmission clusters were inferred from phylogenetic clustering analysis. RESULTS: Of the 60 subjects analysed, 95% were men, and 73.3% were men who have sex with men (MSM). Six HIV-1 subtypes were identified, including CRF01_AE (46.7%), subtypes B (30%), B' (15%) and G (1.7%), CRF33_01B (1.7%) and CRF34_01B (5%). Primary genotypic resistance was detected in only one (1.7%) subtype B variant. Thirty-one patients (51.7%) were phylogenetically clustered, of whom 90% reported having local risk exposure, compared with 59% of the patients who were not phylogenetically clustered [odds ratio (OR) 6.35, 95% confidence interval (CI) 1.65-23.95]. MSM (OR 5.63, 95% CI 1.17-27.15), high viral load (OR 4.28, 95% CI 1.37-13.36) and young age (OR 0.92, 95% CI 0.85-0.99) were independently associated with clustered individuals. CONCLUSIONS: In Singapore, HIV-1 primary resistance is insignificant; individuals with seroconversion account for about half of onward transmission among recently infected seroconverters. MSM, high viral load and young age are factors that facilitate transmission. Early detection of these individuals is of paramount importance for the prevention of HIV-1 transmission.

Quantitative T-cell interferon-gamma responses to Mycobacterium tuberculosis-specific antigens in active and latent tuberculosis.

The objective was to compare the quantitative T-cell responses measured by the commercial interferon-gamma (IFNgamma) release assays (IGRAs) in active and latent tuberculosis (TB) states. T-cell responses of culture-proven TB cases were compared with those of contacts with positive IGRA results and tuberculin skin tests >or= 15 mm. T-SPOT.TB results in 270 active TB cases and 183 community contacts showed the median spot-forming cells (SFCs) above negative control/2.5 x 10(5) peripheral blood mononuclear cells to be 27 (-1 to 203) vs 10 (-2 to 174) in response to ESAT-6 (p < 0.001); and 37 (0 to 293) vs 13 (0 to 225) to CFP-10 (p < 0.001). The median IFNgamma levels (antigen minus nil control) as measured by QuantiFERON-TB Gold In-tube in 270 cases and 142 contacts in congregate settings was 2.3 IU/ml (-0.58 to 31.44) vs 1.7 IU/ml (0.35 to 26.51, p = 0.98). Quantitative T-cell responses as measured by the T-SPOT.TB may indicate mycobacterial burden and disease activity, but cannot be used to discriminate active from latent TB.

Community-based study of acne vulgaris in adolescents in Singapore.

BACKGROUND: There are few studies on the prevalence of acne vulgaris among Asian teenagers. OBJECTIVES: To determine the epidemiology of acne in teenagers in Singapore. METHODS: A community-based cross-sectional study in 1045 adolescents aged 13-19 years. RESULTS: Of these respondents, 88% identified themselves as having acne. Eight hundred and six of these respondents were examined by a dermatologist, and 51.4% were classified as having mild acne, 40% moderate acne and 8.6% severe acne. Isolation of Propionibacterium acnes was attempted in 262 subjects. Cultures were positive in 174 subjects, giving an isolation rate of 66.4%. Antibiotic-resistant strains of P. acnes were detected in 26 isolates (14.9%). Eleven of these 26 subjects (42%) had previously been treated or were presently on antibiotic treatment for acne, but the other 58% of students who had antibiotic-resistant strains of P. acnes did not give a history of prior antibiotic therapy. Teenagers expressed psychological distress over acne, and believed that hormonal factors, diet and hygiene were important factors in causing acne. CONCLUSIONS: There is a need for accessible, accurate education on acne and its appropriate treatment.

Prevalence of and risk factors for nasal colonization with Staphylococcus aureus among human immunodeficiency virus-positive outpatients in Singapore.

We studied the prevalence of and risk factors for Staphylococcus aureus nasal colonization in HIV-positive outpatients in Singapore. Overall prevalence was 23% (45 of 195), with 3% (6 of 195) being MRSA. Recent antibiotic use and hospitalization were independent predictors of MRSA colonization. Isolates were genotypically identical to our hospital's inpatient circulating strain.

Laboratory safety aspects of SARS at Biosafety Level 2.

The severe acute respiratory syndrome (SARS)-associated coronavirus causes severe disease, is transmissible to the community and there is no effective prophylaxis or treatment--perhaps fulfilling the criteria for biohazard group 3 or 4. The recommendation to use Biosafety Level (BSL)3 practices within a BSL2 environment appears to have been a practical decision based on available resources; most diagnostic laboratories operate at BSL2. Safety is achieved with controls in administration, engineering and personal protective equipment/behaviour. At the heart of every safety policy is a risk assessment based on the exact manipulations employed. Excessive administrative and engineering controls are less important than the training and personal attitudes, abilities and understanding of the staff. The SARS outbreak focused our attention on the safety aspects of common mundane tasks, such as decapping blood tubes. Laboratories often claim they follow certain practices but casual observation does not always support these claims. Guidelines differed and created uncertainty. This was stressful for laboratory staff held accountable for their implementation. Attempts to categorise risks and their management into neatly wrapped parcels are attractive, but closer inspection reveals a subjective element that allows doubt to creep in with varying interpretations of the literature. Staff most at risk were those handling respiratory samples. Staff receiving samples via pneumatic tubes had least control over their exposure and were potentially exposed to aerosols from leaking samples. Risk assessment remains a balance between cost and benefit.

Chronic monoarthritis of the knee in systemic lupus erythematosus.

We describe a middle-aged lady with systemic lupus erythematosus who presented with chronic left knee monoarthritis without constitutional symptoms. The histology of synovial tissue taken at arthroscopy showed acute inflammation and Erysipelothrix rhusiopathiae, identified with some difficulty, was isolated from the enrichment broth only. Blood cultures were negative. Her history revealed significant exposure to pond fish. She responded well to intravenous penicillin and remains well 12 months later.

Prevalence of Candida species, including Candida dubliniensis, in Singapore.

We present data on the prevalence of Candida species isolated from inpatients in three Singapore hospitals and from vaginal samples collected at community clinics. Strikingly, approximately 20% of the isolates from blood and vaginal samples were fluconazole-resistant species. By analyzing species-specific gene sequence signatures, we identified Candida dubliniensis from both groups of patients.

First reported isolation of Cryptococcus neoformans var. gattii from a patient in Singapore.

Cryptococcal meningitis has long been known to afflict immunocompetent patients in Singapore. We report the first identification of an isolate of Cryptococcus neoformans var. gattii from a Singaporean resident; this variety can cause invasive disease in the immunocompetent. Meningitis in a traveler returning from this area may be cryptococcal.